Riverbed sediments have been identified as temporary and long-term accumulation sites for microplastic particles (MPs), but the relocation and retention mechanisms in riverbeds still need to be better understood. In this study, we investigated the depth-specific occurrence and distribution (abundance, type, and size) of MPs in river sediments down to a depth of 100 cm, which had not been previously investigated in riverbeds. In four sediment freeze cores taken for the Main River (Germany), MPs (≥ 100 µm) were detected using two complementary analytical approaches (spectroscopy and thermoanalytical) over the entire depth with an average of 21.7 ± 21.4 MP/kg or 31.5 ± 28.0 mg/kg. Three vertical trends for MP abundance could be derived, fairly constant in top layers (0-‍30 cm), a decrease in middle layers (30-60 cm), and a strong increase in deep layers (60-100 cm). The dominant polymer types were polyethylene (PE), polypropylene (PP), and polystyrene (PS). Polyethylene terephthalate (PET) and PP were also found in deep layers, albeit with the youngest age of earliest possible occurrence (EPO age of 1973 and 1954). The fraction of smaller-sized MPs (100-500 µm) increased with depth in shallow layers, but the largest MPs (> 1 mm) were detected in deep layers. Based on these findings, we elucidate the relationship between the depth-specific MP distribution and the prevailing processes of MP retention and sediment dynamics in the riverbed. We propose some implications and offer an initial conceptual approach, suggesting the use of microplastics as a potential environmental process tracer for driving riverbed sediment dynamics.

Immunotherapy targeted to immune checkpoint inhibitors, such as the program cell death receptor (PD-1) and its ligand (PD-L1), has revolutionized cancer treatment. However, it is now well-known that PD-1/PD-L1 immunotherapy response is inconsistent among patients. The current challenge is to customize treatment regimens per patient, which could be possible if the PD-1/PD-L1 expression and dynamic landscape are known. With positron emission tomography (PET) imaging, it is possible to image these immune targets non-invasively and system-wide during therapy. A successful PET imaging tracer should meet specific criteria concerning target affinity, specificity, clearance rate and target-specific uptake, to name a few. The structural profile of such a tracer will define its properties and can be used to optimize tracers in development and design new ones. Currently, a range of PD-1/PD-L1-targeting PET tracers are available from different molecular categories that have shown impressive preclinical and clinical results, each with its own advantages and disadvantages. This review will provide an overview of current PET tracers targeting the PD-1/PD-L1 axis. Antibody, peptide, and antibody fragment tracers will be discussed with respect to their molecular characteristics and binding properties and ways to optimize them.

Radon, a natural radioactive gas, serves as a valuable tracer in geophysical research and atmospheric science such as detecting stress induced signal in bedrock. However, the conventional radon monitoring methods often lack the sensitivity required to accurately capture such signals. This limitation, coupled with interference from meteorological effects, poses challenges in distinguishing genuine stress-induced signals. In this study, we propose a novel approach utilizing radon concentration gradients at the soil-air interface to enhance sensitivity and detect stress induced radon signals more effectively. Drawing from pressure diffusion models, we demonstrate how seismic stress accumulation in bedrock alters radon profiles in the sub-soil, providing insights into the mechanisms underlying stress-induced radon variations. Building upon this theoretical framework, we introduce the \"Bhabha Radon Observatory for Seismic Application (BhaROSA),\" a remote sensing, solar-powered radon observatory designed for widespread deployment and continuous unattended monitoring for big database generation. Field experiments comparing BhaROSA\'s performance to conventional soil probe techniques validate and confirm the superior sensitivity in line with theoretical predictions. This innovative approach holds promise for improving our understanding of stress dynamics in bedrock and has potential applications in various geophysical and atmospheric science such as earthquake precursory research, geo-genic radon potential and risk assessment. To progress, we propose international alliance and application of deep learning to a big database of precursor signals, which may lead to more informed conclusions on earthquake predictability-an enduring and unsolved challenge for humanity.

Effectively managing water resources in karst systems requires a thorough understanding of their general conduit network along with their seasonal dynamics. Their investigation has involved well construction or several advanced natural tracer data, most of which are not always available. Hence, this work showcases a pragmatic approach that makes use of basic hydrochemical variables of springs with coarse temporal resolution in characterising a karst system. In this study\'s example, physicochemical variables like major ion concentrations/ratios, Electrical Conductivity (EC), pH and water temperature (Tw) were measured on 20-day basis for a hydrological year at the Louros Catchment, Greece. We further performed the frequency distribution and variation analysis of EC and Tw, principal component analysis (PCA), scatter plots of carbonate ions vs sulphate and hydrochemographs to determine relevant hydrochemical processes and hydrogeological features. PCA and the scatter plots showed that the simple-type upper karst level is entirely dominated by carbonate dissolution, whereas the complex-type middle and lower levels also involve gypsum and dolomite dissolution. Presence of mixing between karst units was also detected. EC and Tw analyses revealed the degree of karstification of different units and relative depths of flow systems. Hydrochemographs reflected the seasonality of limestone and gypsum dissolution\'s contributions linked to the dominant flow type (conduit vs diffuse). This study thus was able to demonstrate the usefulness of such holistic hydrochemical analyses to better understand karst systems. Given their cost-effectiveness, they can be easily applied to any understudied karst system worldwide.

Few studies have examined the N kinetics of individual feeds with stable isotope tracing. We hypothesized that N partitioning to milk and excreta pools as well as the rates of the processes that drive this partitioning would differ for alfalfa silage, corn silage, corn grain, and soybean meal. Feed ingredients were endogenously labeled with 15N and included in 4 diets to create treatments with the same dietary composition and different labeled feed. Diets were fed to 12 late-lactation dairy cows for 4 d (96 h) and feces, urine, and milk collection proceeded during the 4 d of 15N enrichment and for 3 d (80 h) after cessation of label feeding. Nonlinear models of 15N enrichment and decay were fit to milk (MN), urine (UN), and fecal N (FN) in R with the nlme package and feed-specific parameter estimates were compared. The estimated proportions of feed N that were excreted in feces supported our understanding that N from soybean meal and corn grain is more digestible than N from alfalfa and corn silage. Estimates for the N partitioning between milk (MN) and urine (UN) from the 2 concentrate feeds (soybean meal and corn grain) indicated that UN:MN ratios were less than or equal to 1:1 indicating either more or equal nitrogen partitioning to milk compared with urine. It is important to maintain factual accuracy in representing the results rather than implying a desired outcome unsupported by the data. In contrast, UN:MN ratios for forage feeds (corn and alfalfa silage) were > 1:1, indicating more N partitioning to urine than milk. The modeled proportion of total FN that originated from feed N was 82.2% which is in line with previous research using a similar 15N measurement timeframe. However, the proportion of urinary and MN originating from feed N was much lower (60.5% for urine, 57.9% for milk), suggesting that approximately 40% of urinary and MN directly originate from body N sources related to protein turnover.

OBJECTIVE: Regional lymph node (LN) volume decreases after neoadjuvant therapy, requiring a tracer for more accurate detection. Nano-carbon tracer is a third-generation tracer with several advantages, but its use for LN detection after neoadjuvant chemoradiotherapy for middle and low rectal cancer remains unclear. Therefore, this study investigated the effects and safety of anoscope-guided subrectal injections of nano-carbon suspension in this patient population.
METHODS: This study retrospectively reviewed the medical records of 45 patients with middle and low rectal cancer admitted to our institution from March 2019 to March 2022. All patients received preoperative neoadjuvant chemotherapy and radiotherapy and were divided into nano-carbon injection (n = 23; anoscope-guided injections of nano-carbon suspension in the rectal submucosa 2 cm above the dentate line 24 h preoperatively) and control (n = 22; directly underwent surgery) groups. The LN detection and complication rates were compared between the groups.
RESULTS: The total and mean numbers of LNs and small LNs and the number of patients with > 12 LNs were significantly higher in the nano-carbon injection group than in the control group. The total number of positive LNs and LN metastasis did not differ between the groups, nor did the anastomotic leakage, bleeding, stenosis, and abscess occurrence rates.
CONCLUSIONS: Anoscope-guided nano-carbon lymphatic tracing increased the LN detection rate, caused less trauma, and resulted in fewer postoperative complications than the direct surgical procedure. Thus, it is an effective, safe, and practical method that may improve dissections and the postoperative pathological staging accuracy.

Nitric oxide (NO) plays a pivotal role as a biological signaling molecule, presenting challenges in its specific detection and differentiation from other reactive nitrogen and oxygen species within living organisms. Herein, a 18F-labeled (fluorine-18, t1/2 = 109.7 min) small-molecule tracer dimethyl 4-(4-(4-[18F]fluorobutoxy)benzyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate ([18F]BDHP) is developed based on the dihydropyridine scaffold for positron emission tomography (PET) imaging of NO in vivo. [18F]BDHP exhibits a highly sensitive and efficient C-C cleavage reaction specifically triggered by NO under physiological conditions, leading to the production of a 18F-labeled radical that is readily retained within the cells. High uptakes of [18F]BDHP are found within and around NO-generating cells, such as macrophages treated with lipopolysaccharide or benzo(a)pyrene. MicroPET/CT imaging of arthritic animal model mice reveals distinct tracer accumulation in the arthritic legs, showcasing a higher distribution of NO compared with the control legs. In summary, a specific radical-generating dihydropyridine tracer with a unique radical retention strategy has been established for the marking of NO in real-time in vivo.

OBJECTIVE: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer.
METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer.
RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes.
CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

BACKGROUND: Both in clinical routine and in preclinical research, the established standard procedure for the final purification of radiometal-labeled peptide radiopharmaceuticals is cartridge-based reversed-phase (RP) solid phase extraction (SPE). It allows the rapid and quantitative separation of the radiolabeled peptide from hydrophilic impurities and easy integration into automated synthesis procedures. However, product elution from RP cartridges necessitates the use of organic solvents and product recovery is sometimes limited. Thus, an alternative purification method based on commercially available size exclusion cartridges was investigated.
RESULTS: Since most peptide radiopharmaceuticals have a molecular weight > 1 kDa, Sephadex G10 cartridges with a molecular size cut-off of 700 Da were used for the final purification of a broad palette of 68Ga-, 64Cu- and 99mTc-labeled experimental peptide radiotracers as well as the clinically relevant ligand PSMA-617. Results (radiochemical purity (RCP, determined by ITLC), recovery from the solid support) were compared to the respective standard RP-SPE method. Generally, retention of unreacted 68Ga, 64Cu and 99mTc salts on the G10 cartridges was quantitative up to the specified elution volume (1.2 mL) for 68Ga and 99mTc and 99.6% for 64Cu. Even at increased elution volumes of 1.5-2 mL, RCPs of the eluted 68Ga- and 99mTc -radiopeptides were > 99%. For all peptides with a molecular weight ≥ 2 kDa, product recovery from the G10 cartridges was consistently > 85% upon respective adjustment of the elution volume. Product recovery was lowest for [68Ga]Ga-PSMA-617 (67%, 1.2 mL to 84%, 2 mL). The pH of the final product solution was found to be volume-dependent (1.2 mL: pH 6.3; 1.5 mL: pH 5.9; 2 mL: pH 5.5). Notably, the G10 cartridges were reused up to 20 times without compromising performance, and implementation of the method in an automated radiosynthesis procedure was successful.
CONCLUSIONS: Overall, size exclusion purification yielded all peptide radiopharmaceuticals in excellent radiochemical purities (> 99%) in saline within 10-12 min. Although product recovery is marginally inferior to classical SPE purifications, this method has the advantage of completely avoiding organic solvents and representing a cost-effective, easy-to-implement purification approach for automated radiotracer synthesis.